Cerebral amyloid angiopathy – Definition – Description – Causes

Definition
Cerebral amyloid angiopathy (CAA) is also known as congophilic angiopathy or cerebrovascular amyloidosis. It is a disease of small blood vessels in the brain in which deposits of amyloid protein in the vessel walls may lead to stroke, brain hemorrhage, or dementia. Amyloid protein resembles a starch and is deposited in tissues during the course of certain chronic diseases.

Description
CAA may affect patients over age 45, but is most common in patients over age 65, and becomes more common with increasing age. Men and women are equally affected. In some cases, CAA is sporadic but it may also be inherited as an autosomal dominant condition (a form of inheritance in which only one copy of a gene coding for a disease need be present for that disease to be expressed; if either parent has the disease, a child has a 50% chance of inheriting the disease). CAA is responsible for 5-20% of brain hemorrhage, and up to 30% of lobar hemorrhages localized to one lobe of the brain. CAA may be found during an autopsy in over one-third of persons over age 60, even though they may not have had brain hemorrhage, stroke, or other manifestations of the disease during life. In Alzheimer's disease, CAA is more common than in the general population, and may occur in more than 80% of patients over age 60.

Causes
The cause of cerebral amyloid angiopathy is unknown. Persons with this condition have deposits of amyloid protein in the walls of the brain arteries. The protein is usually not deposited anywhere else in the body.

The major risk factor is increasing age. The rate of the condition is much greater in those older than 60.
Symptoms

Cerebral amyloid angiopathy can cause bleeding into the brain, usually in the outer parts of the brain, called the lobes, and not the deep areas. Symptoms occur because bleeding in the brain harms brain tissue. If there is a lot of bleeding, immediate symptoms occur and resemble a stroke. Such symptoms include:

    * Drowsiness
    * Headache (usually on a specific part of the head)
    * Neurologic changes that may start suddenly, including:
    * Confusion, delirium
    * Double vision, decreased vision
    *  Sensation changes or loss of sensation in an area
    *  Speech difficulties
    * Weakness or paralysis
    * Seizures
    * Stupor or coma (rarely)
    * Vomiting

Some bleeds are very small and occur in different parts of the brain over many months. Symptoms can include:

    * Episodes of confusion
    * Headaches that come and go
    * Loss of mental function (dementia)
    * Sensation changes (unusual sensations) that come and go
    * Seizures

Diagnosis
As in most neurologic diseases, diagnosis is made most often from the patient's history, with careful inquiry into family history and the patient's onset and pattern of symptoms, as well as neurologic examination. Brain computed tomography scan (CT) or magnetic resonance imaging (MRI) may identify lobar hemorrhage, stroke, or petechial hemorrhages, and are important in excluding arteriovenous malformation, brain tumor, or other causes of hemorrhage. Angiography (x-ray study of the interior of blood vessels and the heart) is not helpful in diagnosis of CAA, but may be needed to exclude aneurysm. Brain biopsy (surgical removal of a small piece of brain tissue) may show characteristic amyloid deposits, but is rarely performed, as the risk may not be justifiable in the absence of effective treatment for CAA. If diagnosis is uncertain, biopsy may be needed to rule out conditions which are potentially treatable. Definite diagnosis requires microscopic examination of brain tissue, either at biopsy, at autopsy, or at surgery when brain hemorrhage is drained. Lumbar puncture to examine cerebrospinal fluid proteins may show characteristic abnormalities, but is not part of the routine exam. In familial forms, genetic analysis may be helpful.

CAA with hemorrhage must be distinguished from other types of brain hemorrhage. In CAA, hemorrhage typically occurs in the lobar region, often ruptures into the subarachnoid space between the brain and its coverings, and occurs at night. In hemorrhage related to high blood pressure, hemorrhage is usually deeper within the brain, ruptures into the ventricles or cavities deep inside the brain, and occurs during daytime activities. Other causes of brain hemorrhage are arteriovenous malformations, trauma, aneurysms, bleeding into a brain tumor, vasculitis (inflammation of blood vessels), or bleeding disorders.

Treatment
Although there is no effective treatment for the underlying disease process of CAA, measures can be taken to prevent brain hemorrhage in patients diagnosed with CAA. High blood pressure should be treated aggressively, and even normal blood pressure can be lowered as much as tolerated without side effects from medications. Blood thinners such as Coumadin, antiplatelet agents such as aspirin, or medications designed to dissolve blood clots may cause hemorrhage in patients with CAA, and should be avoided if possible. If these medications are required for other conditions, such as heart disease, the potential benefits must be carefully weighed against the increased risks.

Seizures, or recurrent neurologic symptoms thought to be seizures, should be treated with antiepileptic drugs, although Depakote (sodium valproate) should be avoided because of its antiplatelet effect. Anti-epileptic drugs are sometimes given to patients with large lobar hemorrhage in an attempt to prevent seizures, although the benefit of this is unclear.

Once brain hemorrhage has occurred, the patient should be admitted to a hospital (ICU) for neurologic monitoring and control of increased pressure within the brain, blood pressure control, and supportive medical care. Antiplatelet agents and blood thinners should be discontinued and their effects reversed, if possible. Surgery may be needed to remove brain hemorrhage, although bleeding during surgery may be difficult to control.

CAA may be rarely associated with cerebral vasculitis, or inflammation of the blood vessel walls. In these cases treatment with steroids or immune system suppressants may be helpful. Without tissue examination, vasculitis cannot be diagnosed reliably, and probably coexists with CAA too rarely to justify steroid treatment in most cases.

Prognosis
Since CAA is associated with progressive blood vessel degeneration, and since there is no effective treatment, most patients have a poor prognosis. Aggressive neurosurgical management allows increased survival following lobar hemorrhage, but as of 1998, 20-90% of patients die from the first hemorrhage or its complications, which include progression of hemorrhage, brain edema (swelling) with herniation (downward pressure on vital brain structures), seizures, and infections such as pneumonia. Many survivors have persistent neurologic deficits related to the brain lobe affected by hemorrhage, and are at risk for additional hemorrhages, seizures, and dementia. Prognosis is worse in patients who are older, or who have larger hemorrhages or recurrent hemorrhages within a short time.

Resources
http://medical-dictionary.thefreedictionary.com

http://www.nlm.nih.gov/medlineplus